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Title: Crystal structure of the Rous sarcoma virus intasome

Abstract

Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction. Although structures of the tetrameric integrase–DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers, the architecture of a canonical three-domain integrase bound to DNA remained elusive. In this paper, we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein–DNA and protein–protein contacts that show both conserved and distinct features compared with thosemore » observed for prototype foamy virus integrase. Finally, our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.« less

Authors:
 [1];  [1];  [2];  [3];  [3];  [3];  [1]
  1. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Biochemistry, Molecular Biology and Biophysics. Inst. for Molecular Virology. Masonic Cancer Center
  2. Cornell Univ., Lemont, IL (United States). Advanced Photon Source. Northeastern Collaborative Access Team
  3. Saint Louis Univ., St. Louis, MO (United States). Health Sciences Center. Inst. for Molecular Virology
Publication Date:
Research Org.:
Univ. of Minnesota, Minneapolis, MN (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)
Contributing Org.:
Cornell Univ., Lemont, IL (United States). Advanced Photon Source; Saint Louis Univ., St. Louis, MO (United States)
OSTI Identifier:
1239418
Grant/Contract Number:  
AC02-06CH11357; P41 GM103403; GM109770; AI087098; AI100682
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Volume: 530; Journal Issue: 7590; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; X-ray crystallography; Retrovirus; DNA; DNA-binding proteins

Citation Formats

Yin, Zhiqi, Shi, Ke, Banerjee, Surajit, Pandey, Krishan K., Bera, Sibes, Grandgenett, Duane P., and Aihara, Hideki. Crystal structure of the Rous sarcoma virus intasome. United States: N. p., 2016. Web. doi:10.1038/nature16950.
Yin, Zhiqi, Shi, Ke, Banerjee, Surajit, Pandey, Krishan K., Bera, Sibes, Grandgenett, Duane P., & Aihara, Hideki. Crystal structure of the Rous sarcoma virus intasome. United States. https://doi.org/10.1038/nature16950
Yin, Zhiqi, Shi, Ke, Banerjee, Surajit, Pandey, Krishan K., Bera, Sibes, Grandgenett, Duane P., and Aihara, Hideki. 2016. "Crystal structure of the Rous sarcoma virus intasome". United States. https://doi.org/10.1038/nature16950. https://www.osti.gov/servlets/purl/1239418.
@article{osti_1239418,
title = {Crystal structure of the Rous sarcoma virus intasome},
author = {Yin, Zhiqi and Shi, Ke and Banerjee, Surajit and Pandey, Krishan K. and Bera, Sibes and Grandgenett, Duane P. and Aihara, Hideki},
abstractNote = {Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction. Although structures of the tetrameric integrase–DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers, the architecture of a canonical three-domain integrase bound to DNA remained elusive. In this paper, we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein–DNA and protein–protein contacts that show both conserved and distinct features compared with those observed for prototype foamy virus integrase. Finally, our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.},
doi = {10.1038/nature16950},
url = {https://www.osti.gov/biblio/1239418}, journal = {Nature (London)},
issn = {0028-0836},
number = 7590,
volume = 530,
place = {United States},
year = {Wed Feb 17 00:00:00 EST 2016},
month = {Wed Feb 17 00:00:00 EST 2016}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 64 works
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Figures / Tables:

Extended Data Figure 1 Extended Data Figure 1: Amino acid sequence alignment of RSV, HIV-1, and PFV INs The secondary structure elements for RSV IN are color-coded based on the three IN domains similarly to Fig. 1a. The residue numbering at the top is for RSV IN. For each IN, the black dotsmore » mark every ten residues. This figure was made using ESPript.« less

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A 32,000-Dalton nucleic acid-binding protein from avian retravirus cores possesses DNA endonuclease activity
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Atomic Resolution Structures of the Core Domain of Avian Sarcoma Virus Integrase and Its D64N Mutant ,
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Retroviral intasome assembly and inhibition of DNA strand transfer
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The Mu transpososome structure sheds light on DDE recombinase evolution
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Structural basis for retroviral integration into nucleosomes
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Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function
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Programmable RNA targeting by bacterial Argonaute nucleases with unconventional guide binding and cleavage specificity
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Host ANP32A mediates the assembly of the influenza virus replicase
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A mutant murine leukemia virus with a single missense codon in pol is defective in a function affecting integration.
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Multiple Integrase Functions Are Required to Form the Native Structure of the Human Immunodeficiency Virus Type I Intasome
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The free energy landscape of retroviral integration
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Structures of a RAG-like transposase during cut-and-paste transposition
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Structure of a P element transposase–DNA complex reveals unusual DNA structures and GTP-DNA contacts
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Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition
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Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome
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Structural basis for strand-transfer inhibitor binding to HIV intasomes
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Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration
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Retrotransposon targeting to RNA polymerase III-transcribed genes
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Structural Implications of Genotypic Variations in HIV-1 Integrase From Diverse Subtypes
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Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer.
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The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study
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The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study
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Prototype foamy virus integrase is promiscuous for target choice
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Differential assembly of Rous sarcoma virus tetrameric and octameric intasomes is regulated by the C-terminal domain and tail region of integrase
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Structural Implications of Genotypic Variations in HIV-1 Integrase From Diverse Subtypes
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Structural Insights on Retroviral DNA Integration: Learning from Foamy Viruses
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